Nuclear magnetic resonance study of lung water compartments in the rat.
Nuclear magnetic resonance transverse relaxation time (T2) was previously measured in studies of lung water. The T2 decay curves for peripheral lung tissue were found to be multiexponential with two T2 components: T2 fast (T2f) and T2 slow (T2s). This behavior was explained by the compartmentalization of water, in which the protons of water are restricted and do not undergo rapid exchange between the compartments. We investigated the origin of the water for these T2 components using excised rat lungs. The effect of magnetic field inhomogeneity due to air-tissue interfaces was examined by degassing some lungs. The contribution of intravascular water was examined by perfusing the lungs with oil or NaCl solutions. Degassing produced a greater increase in the T2f than the T2s component, indicating that the water in the alveolar walls exposed to air spaces contributed to the T2f. Perfusion with oil decreased the T2s, indicating that intravascular water contributed to the T2s component. The effects of intravascular osmotic pressure on the T2f and T2s components suggest that intracellular water is related to the T2f component.


Antipsychotic-induced extrapyramidal syndromes in psychiatric practice: a case-control study.
While several clinical trials showed that atypical antipsychotics have a low risk of extrapyramidal side effects (EPS), this observation is not undisputed. This study compared the risk of EPS between specific subgroups of antipsychotics. Using the automated dispensing records of a large psychiatric hospital in The Netherlands, we defined cases as first-time users of anticholinergic antiparkinson drugs. Controls were all patients with no recorded use of such medication. Cases and controls were compared with regard to previous use of antipsychotics and relevant co-factors. Out of 1403 patients, we identified 105 cases and 330 controls. Compared to non-users, antipsychotic-users were 10 times more likely to start with anticholinergic antiparkinson medication (adjusted odds ratio: 10.1; 95 CI 4.6-22.3). Depot and non-depot antipsychotics had similar adjusted odds ratios of 10.9 (95 CI 3.7-32.6) and 8.8 (95% CI 3.8-20.4) respectively. Low and high potency antipsychotics gave odds ratios of 3.0 (95% CI 0.9-10.3) versus 10.8 (95% CI 4.7-25.1). Classical and atypical antipsychotics showed comparable odds ratios: 10.0 (95% CI: 4.4-22.5) versus 8.0 (95% CI: 2.6-24.5). Applied doses of classical and atypical antipsychotic drugs were much lower and more equivalent than those used in previous clinical trials. Low potency antipsychotics had a much lower risk of EPS than other antipsychotics. However, we did not corroborate the reduced risk with atypical antipsychotics observed in several clinical trials. This discrepancy may result from the high and non-equivalent doses of classical antipsychotics used in many of these trials.


Evolution of two-gap behavior of the superconductor FeSe1-x.
The superfluid density, rho{s}, of the iron chalcogenide superconductor, FeSe1-x, was studied as a function of pressure by means of muon-spin rotation. The analysis of rho{s}(T) within the two-gap scheme reveals that the effect on both, the transition temperature T{c} and rho{s}(0), is entirely determined by the band(s) where the large superconducting gap develops, while the band(s) with the small gap become practically unaffected.


Immunocytochemical and ultrastructural identification of mitotic cells in the pituitary gland of ovariectomized rats.
Light microscopic immunocytochemistry was utilized on plastic-embedded, acrolein-fixed pituitary glands from intact rats and rats killed 14 days after ovariectomy to determine which cell types were undergoing cell division. A significant increase in the number of cell divisions in anterior pituitary cells was seen in ovariectomized rats compared to intact controls. Most of the dividing cells in ovariectomized rats were immunocytochemically identified as gonadotrophs, but dividing somatotrophs and non-immunoreactive cells were also found. All of the dividing gonadotrophs stained with both anti-FSH beta and anti-LH beta. These cells were large and ovoid with plentiful vesiculated rough endoplasmic reticulum and a single population of granules with a mean diameter of 200 nm. Many of the dividing cells which were not immunoreactive with any of the antisera employed contained small granules, 100 nm in diameter, but the content of these granules was not determined.


Evaluating a 10-Week Family-Focused E-Health Healthy Lifestyle Program for School-Aged Children with Overweight or Obesity: A Randomized Controlled Trial Study Protocol.
E-Health childhood obesity treatment interventions may serve as favorable alternatives to conventional face-to-face programs. More studies are needed to evaluate the effectiveness of such interventions beyond immediately post-program completion, including exploring program features impacting effectiveness. This randomized controlled trial with a qualitative component and waitlisted control group will evaluate the effectiveness of a 10-week family-focused e-Health program for school-aged children with overweight/obesity and explore the experience of families completing the program. The primary outcome is the change in BMI z-score and will be assessed from baseline to 10 weeks. Secondary outcomes include (the change in) waist circumference, dietary intake, physical activity, quality of life, and experiences, and will be assessed at baseline, post-10 weeks, and/or immediately, 3-, 6-, and/or 12-months post-program completion. Independent t-tests will be used to compare the differences in means and analyses of variances (ANOVAs) will be conducted to investigate the impact of the program or of being waitlisted and the effect size of the program on quantitative outcome measures. Reflexive thematic analysis will be used with qualitative data. Findings from this study are expected to provide learnings to upscale conventional childhood obesity treatment services, in the hopes of curbing the rising rate of childhood obesity.


Validation of reference genes of grass carp Ctenopharyngodon idellus for the normalization of quantitative real-time PCR.
Expression of four reference genes of grass carp, including beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA (18S) and elongation factor-1 alpha (EF1alpha), was studied in tissues of normal individuals and bacteria-infected individuals. EF1alpha had the most stable expressions followed by 18S rRNA then GAPDH; ACTB had the least stability. After being infected with bacteria, the grass carp showed minimal changes in expression levels of EF1alpha in the liver and head kidney, while ACTB had the most stable expressions in spleen but the least stable in liver. EF1alpha is thus the optimal reference gene in quantitative real-time PCR analysis to quantitate the expression levels of target genes in tissues of grass carp.


VMAT-SBRT planning based on an average intensity projection for lung tumors located in close proximity to the diaphragm: a phantom and clinical validity study.
The aim of the this study was to validate the use of an average intensity projection (AIP) for volumetric-modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT) planning for a moving lung tumor located near the diaphragm. VMAT-SBRT plans were created using AIPs reconstructed from 10 phases of 4DCT images that were acquired with a target phantom moving with amplitudes of 5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each phase was recalculated and the doses were accumulated by using the phantom position known for each phase. For 10 patients with lung tumors, a deformable registration was used to generate 4D dose distributions. Doses to the target volume obtained from the AIP plan and the 4D plan were compared, as were the doses obtained from each plan to the organs at risk (OARs). In both phantom and clinical study, dose discrepancies for all parameters of the dose volume (D(min), D(99), D(max), D(1) and D(mean)) to the target were <3%. The discrepancies of D(max) for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the discrepancy of the D(max) was as much as 9.6 Gy for liver and 5.7 Gy for stomach. Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose, but doses to the OARs with large respiratory motion were underestimated with the AIP approach.


Integrating positive psychology into health-related quality of life research.
Positive psychology is an increasingly influential force in theory and research within psychology and many related fields, including behavioral medicine, sociology, and public health. This article aims to review the ways in which positive psychology and health-related quality of life (HRQOL) research currently interface and to suggest fruitful future directions. This article reviews the basic elements of positive psychology and provides an overview of conceptual and empirical links between positive psychology and HRQOL. The role of one central aspect of positive psychology (meaning) within HRQOL is highlighted, and unresolved issues (e.g., lack of definitional clarity) are discussed. Some research on HRQOL has taken a positive psychology perspective, demonstrating the usefulness of taking a positive psychology approach. However, many areas await integration. Once conceptual and methodological issues are resolved, positive psychology may profitably inform many aspects of HRQOL research and, perhaps, clinical interventions to promote HRQOL as well.


Nanoscale Resolution 3D Printing with Pin-Modified Electrified Inkjets for Tailorable Nano/Macrohybrid Constructs for Tissue Engineering.
Cells respond to their microenvironment, which is of a size comparable to that of the cells. The macroscale features of three-dimensional (3D) printing struts typically result in whole cell contact guidance (CCG). In contrast, at the nanoscale, where features are of a size similar to that of receptors of cells, the response of cells is more complex. The cell-nanotopography interaction involves nanoscale adhesion localized structures, which include cell adhesion-related particles that change in response to the clustering of integrin. For this reason, it is necessary to develop a technique for manufacturing tailorable nano/macrohybrid constructs capable of freely controlling the cellular activity. In this study, a hierarchical 3D nano- to microscale hybrid structure was fabricated by combinational processing of 3D printing and electrified inkjet spinning via pin motions. This method overcomes the disadvantages of conventional 3D printing, providing a novel combinatory technique for the fabrication of 3D hybrid constructs with excellent cell proliferation. Through a pin-modified electrified inkjet spinning, we have successfully fabricated customizable nano-/microscale hybrid constructs in a fibrous or mesh form, which can control the cell fate. We have conducted this study of cell-topography interactions from the fabrication approach to accelerate the development of next-generation 3D scaffolds.


Central American ants of the genus Megalomyrmex Forel (Hymenoptera: Formicidae): six new species and keys to workers and males.
Megalomyrmex Forel is a distinctive lineage of Neotropical ants, some of which are specialized parasites or predators of the fungus-growing ants Attini. Here we review and key the Central American fauna. Six new species are described from both female castes: M. brandaoi sp. n., M. fungiraptor sp. n., M. longinoi sp. n., M. milenae sp. n., M. megadrifti sp. n. and M. osadrifti sp. n. A worker-based key to all Central American species is presented, and all species are illustrated. Megalomyrmex drifti Kempf is redescribed and the first descriptions of queens for M. miri Brandão and M. foreli Emery are provided. New biological information, several new geographic records, and a discussion of the species-group schema of Brandão (1990) are presented. The male sex of Megalomyrmex is diagnosed at the genus-level and keyed to species for the Central American fauna, where known. The male of each species treated in the key is diagnosed, described, or redescribed. Males are known for fourteen out of twenty total Central American Megalomyrmex species. A distinct but unassociated male is described and keyed (M. male 01). The males of M. miri Brandão and M. wettereri Brandão are described for the first time, and the distinctness of these two species is confirmed. One potential synapomorphy of Megalomyrmex present in males and workers is the presence of a carina which posteriorly delimits the basalmost region of the petiolar dorsum.


Evaluating Practice-Based Learning.
Practice-based learning is an essential aspect of nursing education, and evaluating this form of learning is vital in determining whether students have the competence required to enter nursing practice. However, limited knowledge exists about the influences that shape how competence development is recognized in nursing programs. The purpose of this study was to explore the evaluation of practice-based learning from the students' standpoint. A qualitative design based on institutional ethnography was used to investigate evaluation of practice-based learning with students, preceptors, and faculty in a preceptorship practicum. The findings revealed how work associated with evaluation was organized by coexisting and often disparate influences within a nursing program and the workplaces where learning took place. The implications and recommendations of the inquiry are intended to encourage dialogue and action among stakeholders from education and practice to improve evaluation practices in preparing new members of the nursing profession. [J Nurs Educ. 2017;56(3):131-138.].


[The Functional Roles and the Potential as Drug Targets of Glycoproteins Regulating Complement and Coagulation Pathways].
Complement (C) activation occurs via three pathways, namely the classical, lectin, and alternative pathways. Intercommunication occurs between the complement and coagulation systems, which can trigger tissue injury and inflammation. Disseminated intravascular coagulation (DIC) is a life-threatening disease characterized by disordered coagulation and systemic inflammation; here, the intercommunication between the complement and coagulation systems contributes to the development of DIC. Extracellular histones, which are contributors to the damage-associated molecular pattern, induce severe thrombosis. C5 is a key molecule in the intercommunication between the complement and coagulation systems and is associated with the development of lethal histone-induced thrombosis. Heparin and chondroitin sulfate (CS) are negatively charged, allowing them to bind to extracellular histones. As the coagulation system is less affected by CS than heparin, CS shows potential as an effective drug for the treatment of patients with DIC who have a high risk of bleeding. Complement receptor type-1-related gene Y (Crry) inhibits the complement pathway via binding to C3b and C4b. Hence, Crry is a potent inhibitor of the classical and alternative C pathways. The expression of Crry is decreased by the endothelial damage induced by extracellular histones. Crry dysfunction promotes the activation of C on the surface of endothelial cells. The prevention of C3 cleavage on endothelial cells might be a useful therapy targeting acute lung injury.


Toxin Fused with SUMO Tag: A New Expression Vector Strategy to Obtain Recombinant Venom Toxins with Easy Tag Removal inside the Bacteria.
Many animal toxins may target the same molecules that need to be controlled in certain pathologies; therefore, some toxins have led to the formulation of drugs that are presently used, and many other drugs are still under development. Nevertheless, collecting sufficient toxins from the original source might be a limiting factor in studying their biological activities. Thus, molecular biology techniques have been applied in order to obtain large amounts of recombinant toxins into Escherichia coli. However, most animal toxins are difficult to express in this system, which results in insoluble, misfolded, or unstable proteins. To solve these issues, toxins have been fused with tags that may improve protein expression, solubility, and stability. Among these tags, the SUMO (small ubiquitin-related modifier) has been shown to be very efficient and can be removed by the Ulp1 protease. However, removing SUMO is a labor- and time-consuming process. To enhance this system, here we show the construction of a bicistronic vector that allows the expression of any protein fused to both the SUMO and Ulp1 protease. In this way, after expression, Ulp1 is able to cleave SUMO and leave the protein interest-free and ready for purification. This strategy was validated through the expression of a new phospholipase D from the spider Loxosceles gaucho and a disintegrin from the Bothrops insularis snake. Both recombinant toxins showed good yield and preserved biological activities, indicating that the bicistronic vector may be a viable method to produce proteins that are difficult to express.


Modification of the TASMIP x-ray spectral model for the simulation of microfocus x-ray sources.
The availability of accurate and simple models for the estimation of x-ray spectra is of great importance for system simulation, optimization, or inclusion of photon energy information into data processing. There is a variety of publicly available tools for estimation of x-ray spectra in radiology and mammography. However, most of these models cannot be used directly for modeling microfocus x-ray sources due to differences in inherent filtration, energy range and/or anode material. For this reason the authors propose in this work a new model for the simulation of microfocus spectra based on existing models for mammography and radiology, modified to compensate for the effects of inherent filtration and energy range. The authors used the radiology and mammography versions of an existing empirical model [tungsten anode spectral model interpolating polynomials (TASMIP)] as the basis of the microfocus model. First, the authors estimated the inherent filtration included in the radiology model by comparing the shape of the spectra with spectra from the mammography model. Afterwards, the authors built a unified spectra dataset by combining both models and, finally, they estimated the parameters of the new version of TASMIP for microfocus sources by calibrating against experimental exposure data from a microfocus x-ray source. The model was validated by comparing estimated and experimental exposure and attenuation data for different attenuating materials and x-ray beam peak energy values, using two different x-ray tubes. Inherent filtration for the radiology spectra from TASMIP was found to be equivalent to 1.68 mm Al, as compared to spectra obtained from the mammography model. To match the experimentally measured exposure data the combined dataset required to apply a negative filtration of about 0.21 mm Al and an anode roughness of 0.003 mm W. The validation of the model against real acquired data showed errors in exposure and attenuation in line with those reported for other models for radiology or mammography. A new version of the TASMIP model for the estimation of x-ray spectra in microfocus x-ray sources has been developed and validated experimentally. Similarly to other versions of TASMIP, the estimation of spectra is very simple, involving only the evaluation of polynomial expressions.


Texas Occurrence of Lyme Disease and Its Neurological Manifestations.
Today, Lyme disease is the most commonly reported tick-borne disease in the United States and Europe. The culprits behind Lyme disease are the Borrelia species of bacteria. In the USA, Borrelia burgdorferi causes the majority of cases, while in Europe and Asia Borrelia afzelii and Borrelia garinii carry the greatest burden of disease. The clinical manifestations of Lyme disease have been identified as early localized, early disseminated, and late chronic. The neurological effects of Lyme disease include both peripheral and central nervous systems involvement, including focal nerve abnormalities, cranial neuropathies, painful radiculoneuritis, meningitis, and/or toxic metabolic encephalopathy, known as Lyme encephalopathy. Given the geographic predominance of Lyme disease in the Northeast and Midwest of the USA, no major studies have been conducted regarding Southern states. Between 2005 and 2014, the Center for Disease Control has reported 582 confirmed cases of Lyme disease in Texas. Because of the potential for increased incidence and prevalence in Texas, it has become essential for research and clinical efforts to be diverted to the region. The Texas A&M College of Veterinary Medicine and Biomedical Sciences Lyme Lab has been investigating the ecology of Lyme disease in Texas and developing a pan-specific serological test for Lyme diagnosis. This report aimed to exposure materials and raise awareness of Lyme disease to healthcare providers.


Early-onset of symptoms and clinical course of Pompe disease associated with the c.-32-13 T > G variant.
Individuals with late-onset Pompe disease (LOPD) and the common c.-32-13 T > G variant are widely thought to have milder, adult-onset disease. This belief, and the consequent low suspicion of clinical involvement in children, has led to delays in diagnosis and treatment initiation in patients with early onset of symptoms. Previous reports of LOPD in children do not include description of the early-onset phenotype. This description of signs and symptoms, some of which are subtle and less known, is important to facilitate prompt identification and appropriate treatment in symptomatic children. Retrospective chart review of a cohort of 84 LOPD patients with the c.-32-13 T > G variant was conducted to identify patients diagnosed clinically (as opposed to through newborn screening) who had clinically documented symptom-onset within the first two years of life. Four patients had early onset of symptoms, with age at onset ranging from 10 days to 20 months. Initial symptoms included delay in achievement of gross motor milestones, signs of proximal muscle weakness, swallow and feeding difficulties, and sleep apnea. Early and characteristic alterations in posture and movement were identified in all patients. Age at diagnosis ranged from 10 months to 26 months. Median age at enzyme replacement therapy (ERT) initiation was 23.5 months. Despite ERT, progression of musculoskeletal involvement and residual muscle weakness was evident in all patients, as evidenced by ptosis, myopathic facies, scoliosis, lumbar lordosis, scapular winging, and trunk and lower extremity weakness. Standardized functional assessments showed gross motor function below age level as measured by the Alberta Infant Motor Scales, the Peabody Developmental Motor Scales-2, the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and the six-minute walk test. Onset of symptoms including delay in achievement of gross motor milestones, signs of proximal muscle weakness, swallow and feeding difficulties, and sleep apnea in the first two years of life is not uncommon in individuals with LOPD and the c.-32-13 T > G variant. Patients with early-onset disease appear to have a more, rapid and severe progression of disease with persistent residual muscle deficits which partially improve with higher doses of ERT. Careful evaluation for specific and characteristic patterns of posture and movement in patients with this variant is necessary to identify those who have early onset of disease. Increased awareness of the early-onset signs and symptoms may also enable early identification of disease onset in children who are diagnosed through newborn screening.


From individual to population level effects of toxicants in the tubicifid Branchiura sowerbyi using threshold effect models in a Bayesian framework.
Effects of zinc were studied in the freshwater worm Branchiura sowerbyi using partial and full life-cycle tests. Only newborn and juveniles were sensitive to zinc, displaying effects on survival, growth, and age at first brood at environmentally relevant concentrations. Threshold effect models were proposed to assess toxic effects on individuals. They were fitted to life-cycle test data using Bayesian inference and adequately described life-history trait data in exposed organisms. The daily asymptotic growth rate of theoretical populations was then simulated with a matrix population model, based upon individual-level outputs. Population-level outputs were in accordance with existing literature for controls. Working in a Bayesian framework allowed incorporating parameter uncertainty in the simulation of the population-level response to zinc exposure, thus increasing the relevance of test results in the context of ecological risk assessment.


Calculations of free energies in liquid and solid phases: fundamental measure density-functional approach.
In this paper, a theoretical description of the free energies and correlation functions of hard-sphere (HS) liquid and solid phases is developed using fundamental measure density-functional theory. Within the framework of Weeks-Chandler-Andersen perturbation theory, free energies of liquid and solid phases with many interaction potentials can be obtained from these characteristics of the HS system within a single theoretical description. An application to the Lennard-Jones system yields liquid-solid coexistence results in good agreement with the ones from simulations.


Testing Alternative Surface Disinfection Agents for Zebrafish (Danio rerio) Embryos.
Pathogen transmission into zebrafish colonies is controlled through vigilant biosecurity practices. One such practice is embryo surface disinfection, which often uses sodium hypochlorite. However, if sodium hypochlorite is used at an inappropriate pH, concentration, or exposure time, zebrafish embryos can experience significant mortality and morbidity. Reagent-grade sodium hypochlorite is often used for embryo surface disinfection because commercial-grade sodium hypochlorite has additional ingredients that may have deleterious effects on the embryo. In addition, chlorine dioxide and the combination of sodium chloride and potassium peroxymonosulfate (SCPP) are effective equipment disinfectants; however, the effects of these chemical agents on zebrafish embryos during surface disinfection are unknown. In this study, we exposed strain 5D zebrafish embryos (ages, 6 and 24 h postfertilization) to 4 chlorine-containing agents (reagent-grade sodium hypochlorite [bleach], commercial-grade sodium hypochlorite [bleach], SCPP, and chlorine dioxide) at either 50- or 100- ppm for 5 or 10 min. All groups were evaluated at 5 d postfertilization for survival, hatching rate, and morphologic defect rate. The experimental group with the highest survival and hatching rates and the lowest morphologic defect rate was the 24-h postfertilization embryos exposed to 50 ppm SCPP for 5 min. The survival, hatching rate, and defect rate did not differ significantly among age-matched controls; however, the hatching rate after exposure to 50 ppm SCPP was significantly higher than that of embryos exposed to 50 ppm reagent-grade sodium hypochlorite for 5 min (100% compared with 23% respectively). SCPP solution may provide an alternative surface disinfectant for zebrafish embryos because it maximizes survival and hatching rates and minimizes morphologic defect rates. However, in vivo efficacy against common zebrafish pathogens requires further testing. Use of chlorine dioxide at 50 ppm or greater is not recommended for zebrafish embryo surface disinfection due to significant mortality among 6 and 24 h postfertilization embryos.


Dispersion Differences and Consistency of Artificial Periodic Structures.
Dispersion differences and consistency of artificial periodic structures, including phononic crystals, elastic metamaterials, as well as periodic structures composited of phononic crystals and elastic metamaterials, are investigated in this paper. By developing a K(ω) method, complex dispersion relations and group/phase velocity curves of both the single-mechanism periodic structures and the mixing-mechanism periodic structures are calculated at first, from which dispersion differences of artificial periodic structures are discussed. Then, based on a unified formulation, dispersion consistency of artificial periodic structures is investigated. Through a comprehensive comparison study, the correctness for the unified formulation is verified. Mathematical derivations of the unified formulation for different artificial periodic structures are presented. Furthermore, physical meanings of the unified formulation are discussed in the energy-state space.


[Does percutaneous nephrolithotripsy (PCNL) affect renal function: assessment with quantitative spect of Tc 99M-DMSA (QDMSA) renal scintigraphy].
The study aimed to quantitatively investigate the effect of PCNL on global and regional function using quantitative single photon emission computerized tomography (SPECT) measurement of Tc-dimercaptosuccinic acid (DMSA) uptake by the kidneys (QDMSA). Seventy nine patients with nephrolithiasis undergoing PCNL were studied by sequential QDMSA examination. There were 42 (53%) males and 37 (47%) females with mean age of 47 +/- 16 years. The initial study was conducted before PCNL procedure and the follow-up studies were performed 1.5-24 months after PCNL. Among 60 of the 79 (76%) patients, in whom PCNL was performed using upper or lower pole access, regional renal function of affected and non-affected pole of operated kidney was calculated separately. There was no statistically significant difference between the uptake of treated kidney before and after PCNL procedure (11.9% +/- 5% vs 11.6% +/- 5%; t = 0.9, p = 0.368). The total renal functional volume of treated kidney was to be slightly decreased from 235cc +/- 62cc to 224cc +/- 59cc (t = 2.7; p = 0.011). The percent of injected dose per ml.. of renal tissue of treated kidney was not affected statistically (0.051 +/- 0.02 vs 0.053 +/- 0.02; t = 0.86, p = 0.296). In the assessment of the regional renal function of treated kidney, a statistically significant decrease in the functional renal volume was revealed at the part which underwent PCNL procedure (91cc +/- 30cc vs 82cc +/- 27cc; t = 2.64, p = 0.013). Regarding percent of injected dose per ml. of renal tissue, no statistically significant difference was found between the part of treated kidney, which underwent PCNL and non-affected area of the same kidney (0.049 +/- 0.02 vs 0.05 +/- 0.02; t = 0.693, p = 0.494). The function of contralateral kidney remained unchanged (13.4% +/- 5.2% vs 13.6% +/- 4.8%; t = 0.68, p = 0.5). Function volume, neither total percent uptake, nor percent of injected dose per ml. of renal tissue were reduced significantly. Further studies with long term follow-up of treated kidney are required.


Multilayered Films Fabricated from Combinations of Degradable Polyamines: Tunable Erosion and Release of Anionic Polyelectrolytes.
This investigation sought to develop methods that permit broad and tunable control over the erosion of multilayered polyelectrolyte assemblies and the release of anionic polymers in physiologically relevant media. We report the fabrication and characterization of multilayered films ~60 nm thick using sodium poly(styrene sulfonate) (SPS) and different combinations of three different hydrolytically degradable polyamines (1-3). We investigated two different approaches to film fabrication: 1) fabrication using solutions comprised of defined mixtures of two different polyamines, and 2) fabrication of films composed of different numbers of layers of two different polyamines. In general, films fabricated using polyamine solutions composed of defined mixtures of two different polyamines had erosion and release profiles that were dictated almost entirely by the most hydrophobic polyamine used to fabricate the films. In contrast, the fabrication of films having different numbers of layers of different polyamines permitted broad and tunable control over film erosion and the release of SPS. For example, films having the architecture (1/SPS)(n)(2/SPS)(m) released SPS with profiles that were intermediate to those of films fabricated exclusively from polymer 1 or polymer 2. Further, we demonstrated that it is possible to exert systematic control over the release of SPS by varying the relative numbers of layers of (1/SPS) or (2/SPS) incorporated into the films. The approaches reported here provide tunable control over the rate of the release of anionic polymers from surfaces coated with ultrathin multilayered films. This work could, with further development, contribute to the design of ultrathin films that permit tunable control over the release and delivery of therapeutically relevant macromolecules, such as proteins or DNA, from surfaces.


Corticotropin-releasing hormone and arginine vasopressin gene transcription in the hypothalamic paraventricular nucleus of unstressed rats: daily rhythms and their interactions with corticosterone.
To drive the daily ACTH secretory rhythm from anterior pituitary corticotropes signals from the circadian clock schedule CRH and, to lesser extent, arginine vasopressin (AVP) release from neuroendocrine terminals. In turn, releasable pools of CRH and AVP in neuroendocrine terminals are sustained by synthetic mechanisms in the medial parvicellular paraventricular nucleus, a critical component of which involves transcribing primary (heteronuclear (hn)) RNA transcripts from their cognate genes. To determine the fundamental daily patterns of ACTH secretagogue gene transcription in unstressed rats, we measured CRH and AVP hnRNA levels at 1- to 4-h intervals throughout the day using in situ hybridization. Crh gene transcription is readily detectable throughout the day, and shows a pronounced rhythm that is temporally correlated with CRH mRNA levels, but is uncoupled from ACTH release. However, avp gene transcription is barely detectable and shows no discernable rhythm. We then performed similar experiments in adrenalectomized rats with or without corticosterone replacement. Corticosterone-dependent mechanisms regulate CRH hnRNA levels at the nadir and peak as well as the onset of nocturnal crh gene transcription. A prominent rhythm of avp hnRNA seen in adrenalectomized animals was dampened by corticosterone. This study shows, first, CRH synthesis in intact animals is maintained by a nocturnal episode of crh gene transcription, parameters of which are modulated by corticosterone-dependent mechanisms; second, circulating corticosterone is sufficient to completely inhibit a daily rhythm of avp gene transcription present in adrenalectomized rats; third, the neural systems that activate crh gene transcription can be uncoupled from those driving ACTH release.


Activation of glomerular mesangial cells by gram-negative bacterial cell wall components.
The cell walls of gram-negative bacteria contain several biologically active components, including lipopolysaccharide (LPS), lipoprotein, and protein 1. The effects of these individual components and a synthetic analog of lipoprotein, TPP, on several activation parameters of glomerular mesangial cells (MC) were examined. Prostaglandin secretion, synthesis of the autogrowth factor, mesangial interleukin-1 (IL-1), and new synthesis of cellular proteins were assessed as markers of MC activation. All bacterial cell wall components evaluated were active in varying degrees as stimulants of prostaglandin secretion. In general, PGE was the predominant product. TPP and protein 1 also induced substantial secretion of thromboxane. Each cell-wall component was effective in stimulating mesangial IL-1 secretion. The activation of MC was associated with the enhanced synthesis of many cellular proteins in addition to IL-1. Stimulation by these bacterial components was dependent on the state of the mesangial cell cycle, because nonproliferating cells did not respond to these factors. Activation of MC by gram-negative bacterial cell wall components, with release of vasoactive prostaglandins and peptide mitogens, may be responsible for some of the glomerular hemodynamic alterations and cellular proliferative events associated with sepsis or chronic bacterial infection.


Interstitial nephritis related to nonsteroidal anti-inflammatory agents and beta-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies.
Acute interstitial nephritis (AIN) is a common pattern of renal injury induced by therapeutic agents. In order to characterize the types of mononuclear leukocytes infiltrating the kidney in drug-induced interstitial nephritis, a panel of monoclonal antibodies (Leu1, Leu3a, OKT8, OKM1, Leu14, OKT17, IL-2) was applied to cryostat sections of 13 renal biopsies (five non-steroidal anti-inflammatory agents (NSAID) (Group I); five beta-lactam antibiotics (Group II), 3 miscellaneous (Group III]. The majority of infiltrating mononuclear leukocytes were Leu1-positive T cells (71.7 +/- 18.7%), followed by monocytes (15.2 +/- 7.7%) and B cells (7.4 +/- 9.1%). Leu3a/OKT8 ratio was 0.954 +/- 0.341. Rare cells reacted with antibody to the interleukin-2 receptor (1.4 +/- 1.2%). No statistically significant differences could be found in the percentages of T lymphocytes, B lymphocytes, monocytes, activated (IL-2+) T cells or Leu3a/OKT8 (helper/suppressor) ratios in the three groups. In Group II, the following pathologic correlations were seen: Leu3a/OKT8 versus interstitial inflammation (R = -0.848), percent Leu3a versus interstitial inflammation (R = -0.818), percent OKT17 versus tubulitis (R = 0.785), percent Leu14 versus tubular atrophy (R = -0.891), and interstitial edema (R = 0.965). Our findings support a role for cellular immune mechanisms in the pathogenesis of AIN related to both NSAIDs and beta-lactam antibiotics.


Favourable outcomes in patients with early-stage non-small-cell lung cancer operated on by video-assisted thoracoscopic surgery: a propensity score-matched analysis.
The video-assisted thoracoscopic surgery (VATS) approach has become a standard for the treatment of early-stage non-small-cell lung cancer (NSCLC). Recently published meta-analyses proved the benefit of VATS versus thoracotomy for overall survival (OS) and reduction of postoperative complications. The aim of this study was to compare early outcomes, long-term survival and rate of postoperative complications of the VATS approach versus thoracotomy. In this retrospective cohort study, we analysed 982 individuals who underwent surgical resection for Stage I-IIA NSCLC between 2007 and 2015. Thirty- and 90-day mortality rates, length of hospital stay, rate of complications and OS were assessed. Propensity score matching was performed to compare 2 groups of patients. Two hundred and twenty-five individuals from the thoracotomy group and 225 patients from the VATS group were matched regarding pTNM, sex, the Charlson comorbidity index, type of resection and histological diagnosis. In the propensity score-matched patient group, the VATS approach was associated with a significant benefit regarding OS (P = 0.042). Although no significant difference was observed (P = 0.14) in the 3-year survival rate of patients who had a thoracotomy versus VATS, the 5-year survival rate among patients with VATS increased significantly (61% vs 78%, P = 0.0081). The adjusted VATS-related hazard ratio for pTNM, sex and age was 0.63 (95% confidence interval 0.40-0.98). The VATS surgical approach also reduced both the rate of postoperative atelectasis (4% for VATS vs 10% for open thoracotomy; P = 0.0052) and the need for blood transfusions (4% vs 12% respectively, P = 0.0054) and significantly shortened the postoperative length of stay (mean 7.25 vs 9.34 days, P < 0.0001). No significant differences in the 30-day mortality (1% vs 1%, P = 0.66) and 90-day mortality (1% vs 1%, P = 0.48) rates were observed. Patients with early-stage NSCLC operated on with VATS had fewer complications, shorter postoperative length of stay and better OS compared to those who were operated on by thoracotomy.


Obesity: pathophysiology and intervention.
Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.


An overview of adjuvants utilized in prophylactic vaccine formulation as immunomodulators.
Development of efficient and cost effective vaccines have been recognized as the primary concern to improve the overall healthcare in a country. In order to achieve this goal, more improved and powerful adjuvants need to be developed. Lacking in the self-adjuvanting immuno-modulatory constituents, vaccines exhibit lower immunogenicity. Combining potent adjuvants with vaccines is the most appropriate method to enhance the efficacy of the vaccines. Hence, this review is focussed on the most potent adjuvants for the formulation of vaccines. Areas covered: This review focuses on Oil-based emulsions, Mineral compounds, Liposomes, Bacterial products, ISCOMs and most recently used nanomaterials as adjuvants for enhancing the antigenicity of vaccines. Furthermore, this review explains the immunological response elicited by various particles. Moreover, case studies are incorporated providing an in depth analyses of various adjuvant-containing vaccines which are currently used. Expert commentary: Enhanced fundamental knowledge about the adjuvants and their immuno-stimulatory capabilities and delivery mechanisms will facilitate the rational designing of prophylactic vaccines with better efficacy.


Entanglement generation and steering implementation in a double-cavity-magnon hybrid system.
We demonstrate a scheme for the generation of bipartite and tripartite entanglement, as well as he implementation of stable and controllable long-distance one-way and asymmetric two-way steering in a cavity-magnon hybrid system. This system consists of a magnon mode and two coupled microwave cavities. The first cavity is driven by a flux-driven Josephson parametric amplifier, which generates squeezed vacuum fields, and is coupled to the other cavity through optical tunneling interaction. The second cavity and magnon mode are coupled through magnetic dipole interaction. We find that under weak coupling between the two cavities, and strong coupling between the second cavity and magnon mode, remote controllable one-way steering and tripartite entanglement can be achieved. Our scheme may have potential applications in quantum information.


Effect of temperature on the spoilage rate of whole, unprocessed crabs: Carcinus maenas, Necora puber and Cancer pagurus.
Shelf life of whole, initially live, crabs depended primarily on the storage conditions and the time at which death occurred. Large differences in the time that individual crab species survived particular storage conditions resulted in wide variations in shelf-life. Bacterial spoilage of Carcinus maenas, Necora puber and Cancer pagurus, measured using aerobic plate counts, indicated that on ice at 4 degrees C whole unprocessed crabs had a shelf life approximately 9-11 days, at 4 degrees C approximately 13-29 days, in simulated supermarket conditions of sale approximately 5-7 days and at 20 degrees C approximately 2-16 days. Storage of whole unprocessed crabs chilled at 4 degrees C considerably extended shelf life compared to crabs stored on ice. Live crabs stored on ice died within 24h, most likely due to thermal shock and their early death was responsible for their more rapid increase in bacterial numbers compared to crabs stored at 4 degrees C. No growth of bacteria occurred in the flesh of live crabs stored at 4 degrees C for between 128 and 504 h. Crab flesh quality deteriorated prior to maximum shelf-life (defined as the time at which bacterial load reached log 5 cfu/g crabmeat) in some instances. The best compromise between high crabmeat yield and long shelf-life is likely to be to transport crabs at 4 degrees C live to market where they could be stored live at 4 degrees C without spoilage for 2 weeks before placed on ice at 4 degrees C, with a potential maximum shelf life of approximately 24 days.


Evaluating trihalomethane content in drinking water on the basis of common monitoring parameters: regression models.
The presence of trihalomethanes (THMs) in potable-water sources is an issue of great interest because of the negative impact THMs have on human health. The objective of this study was to correlate the presence of trihalomethanes with more routinely monitored parameters of water quality, in order to facilitate THM control. Water samples taken at various stages of treatment from a water treatment plant were analyzed for the presence of trihalomethanes with the Fujiwara method. The data collected from these determinations were compared with the values obtained for free-residual-chlorine and combined-residual-chlorine levels as well as standard physico-chemical and microbiological indicators such as chemical oxygen demand (by the KMnO4 method), total chlorophyll, conductivity, pH, alkalinity, turbidity, chlorides, sulfates, nitrates, nitrites, phosphates, ammonia, calcium, magnesium, heterotrophic bacteria count, Pseudomonas spp., total and fecal coliforms, and fecal streptococci. The data from these determinations were compiled, and statistical analysis was performed to determine which variables correlate best with the presence and quantity of trihalomethanes in the samples. Levels of THMs in water seem to correlate directly with levels of combined residual chlorine and nitrates, and inversely with the level of free residual chlorine. Statistical analysis with multiple linear regression was conducted to determine the best-fitting models. The models chosen incorporate between two and four independent variables and include chemical oxygen demand, nitrites, and ammonia. These indicators, which are commonly determined during the water treatment process, demonstrate the strongest correlation with the levels of trihalomethanes in water and offer great utility as an accessible method for THM detection and control.


Traditional Chinese medicine and the search for new antineoplastic drugs.
The experience of traditional Chinese medicine affords a valuable approach in the search for new antineoplastic drugs as illustrated by indirubin from Dang Gui Lu Hui Wan, irisquinone from Iris lactea pallasii and Zhuling polysaccharide from Polyporus umbellata. The application of chemotaxonomic principles to related species of those plants used in folk medicine has also provided an approach which can be used successfully for the development of new drugs. The studies of Cephalotaxus hainanesis and Camptotheca accuminata provide two typical examples in this regard. One must be aware that the experience of traditional Chinese medicine cannot be used without elaborate efforts in many cases. For example, the ancient Chinese ideograph for spleen does not mean spleen in the modern sense, instead it refers to the entire gastrointestinal system. Similarly, the ancient ideograph for kidney does not mean kidney in the modern sense, and can mean the entire endocrine system. Therefore, for the reasonable utilization of traditional Chinese medicine, one must be familiar with its basic concepts and terminology. In addition, one must bear in mind that the term "tumor" in folk medicine is applied to a very wide range of pathological manifestations which sometimes have no relation to the various forms of neoplasia. It is important for drugs and treatments to be analyzed carefully in modern terms to eliminate the false and to utilize the true information. Only in such a way can the experience of traditional medicine be integrated into modern medicine and make its contribution in the advancement of health care in the world.


Urine tropenol ester levels in workers handling tiotropium bromide synthesis: implications for exposure prevention and biomonitoring.
Tropenol ester is a highly toxic anticholinergic substance and an intermediate used in industrial production of the bronchodilator tiotropium bromide. The aim of this study was to systematically test workers involved in its production for tropenol ester in urine to identify any exposure pathways and define additional preventive measures. Twelve workers performing tasks involving potential exposure to tropenol ester were repeatedly monitored at the end of each production cycle. Medical exams revealed no symptoms of acute poisoning with tropenol ester, but biological monitoring of urine showed 36 positive findings in 79 samples, with tropenol ester concentrations ranging between the detection limit of 54 pg/mL and 2160 pg/mL. We managed to establish the cause of only one positive finding, which was a hole in a protective glove, whereas the rest most likely occurred due to human error. Because of this, the plant decided to modify the production process by replacing tropenol ester with a safer intermediate. While it is the safest course of action, there where it cannot be taken, biological monitoring can be very helpful in raising awareness about exposure to toxic substances, including the new ones that have not been studied for their adverse potential.


Early serum biomarker networks in infants with distinct retinochoroidal lesion status of congenital toxoplasmosis.
The present study characterized the early changes in the serum chemokines/cytokine signatures and networks in infants with congenital-toxoplasmosis/(TOXO) as compared to non-infected-controls/(NI). TOXO were subgrouped according to the retinochoroidal lesion status as no-lesion/(NL), active-lesion/(ARL), active/cicatricial-lesion/(ACRL) and cicatricial-lesion/(CRL). The results showed that TOXO display prominent chemokine production mediated by IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and RANTES/CCL5. Additionally, TOXO is accompanied by mixed proinflammatory/regulatory cytokine pattern mediated by IL-6, IFN-γ, IL-4, IL-5 and IL-10. While TNF appears as a putative biomarker for NL and IFN-γ/IL-5 as immunological features for ARL, IL-10 emerges as a relevant mediator in ACRL/CRL. IL-8/CXCL8 and IP-10/CXCL10 are broad-spectrum indicators of ocular disease, whereas TNF is a NL biomarker, IFN-γ and MIG/CXCL9 point out to ARL; and IL-10 is highlighted as a genuine serum biomarker of ACRL/CRL. The network analysis demonstrated a broad chemokine/cytokine crosstalk with divergences in the molecular signatures in patients with different ocular lesions during congenital toxoplasmosis.


The DNA-binding subunit of human transcription factor IID can interact with the TATA box as a multimer.
Transcription initiation from eukaryotic protein-coding genes is a complex process that minimally requires RNA polymerase (pol) II (B) and at least seven general transcription factors. The 38-kDa subunit (TBP) of the human general transcription factor TFIID recognizes the TATA sequence element and initiates the assembly of the other general transcription factors and RNA pol II. It is believed, based on experiments with yeast recombinant protein, that TBP binds as a monomer to DNA. Using purified recombinant human TBP protein we find that TBP interacts with the TATA element as both a monomer and a dimer. The multimeric binding of TBP to DNA revealed by this study has important implications for the role of TBP in transcription initiation and suggests novel mechanisms whereby other transcription factors may interact with a RNA pol II preinitiation complex.


Blood degradation products play a role in cerebral ischemia caused by acute subdural hematoma.
The pathogenesis of ischemic brain lesions with traumatic hematoma is multifactorial. It has been suggested that the presence of subdural hematoma in patients with severe head injury is associated with elevated intracranial pressure and higher mortality. In this study we created acute subdural mass in the rats by injecting 250 microliters of autologous blood and silicone oil into the subdural space. The goal of this study was to determine the effect of subdural hematoma versus silicone oil on the adjacent brain parenchyma. Twenty-four hours after the injection, of the hematoma in the subdural space in rats produced an extensive zone of underlying ischemic damage but silicone oil did not. This study has shown that pressure alone caused by silicone oil is insufficient to cause significant neuronal damage or loss.


Differential expression of appetite-regulating genes in avian models of anorexia and obesity.
Chickens from lines that have been selected for low (LWS) or high (HWS) juvenile body weight for more than 57 generations provide a unique model by which to research appetite regulation. The LWS display different severities of anorexia, whereas all HWS become obese. In the present study, we measured mRNA abundance of various factors in appetite-associated nuclei in the hypothalamus. The lateral hypothalamus (LHA), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), dorsomedial nucleus (DMN) and arcuate nucleus (ARC) were collected from 5 day-old chicks that were fasted for 180 minutes or provided with continuous access to food. Fasting increased neuropeptide Y receptor subtype 1 (NPYR1) mRNA in the LHA and c-Fos in the VMH, at the same time as decreasing c-Fos in the LHA, neuropeptide Y receptor subtype 5 and ghrelin in the PVN, and neuropeptide Y receptor subtype 2 in the ARC. Fasting increased melanocortin receptor subtype 3 (MC3R) expression in the DMN and NPY in the ARC of LWS but not HWS chicks. Expression of NPY was greater in LWS than HWS in the DMN. neuropeptide Y receptor subtype 5 mRNA was greater in LWS than HWS in the LHA, PVN and ARC. Expression of orexin was greater in LWS than HWS in the LHA. There was greater expression of NPYR1, melanocortin receptor subtype 4 and cocaine- and amphetamine-regulated transcript in HWS than LWS and mesotocin in LWS than HWS in the PVN. In the ARC, agouti-related peptide and MC3R were greater in LWS than HWS and, in the VMH, orexin receptor 2 and leptin receptor were greater in LWS than HWS. Greater mesotocin in the PVN, orexin in the LHA and ORXR2 in the VMH of LWS may contribute to their increased sympathetic tone and anorexic phenotype. The results of the present study also suggest that an increased hypothalamic anorexigenic tone in the LWS over-rides orexigenic factors such as NPY and AgRP that were more highly expressed in LWS than HWS in several nuclei.


Tools for Studying Glycans: Recent Advances in Chemoenzymatic Glycan Labeling.
The study of cellular glycosylation presents many challenges due, in large part, to the nontemplated nature of glycan biosynthesis and glycans' structural complexity. Chemoenzymatic glycan labeling (CeGL) has emerged as a new technique to address the limitations of existing methods for glycan detection. CeGL combines glycosyltransferases and unnatural nucleotide sugar donors equipped with a bioorthogonal chemical tag to directly label specific glycan acceptor substrates in situ within biological samples. This article reviews the current CeGL strategies that are available to characterize cell-surface and intracellular glycans. Applications include imaging glycan expression status in live cells and tissue samples, proteomic analysis of glycoproteins, and target validation. Combined with genetic and biochemical tools, CeGL provides new opportunities to elucidate the functional roles of glycans in human health and disease.


Adrenal insufficiency - recognition and management.
Adrenal insufficiency is characterised by inadequate -glucocorticoid production owing to destruction of the adrenal cortex or lack of adrenocorticotropic hormone stimulation. In primary adrenal insufficiency, lack of mineralocorticoids is also a feature. Patients can present with an insidious onset of symptoms, or acutely in adrenal crisis, which requires prompt recognition and treatment. Chronic glucocorticoid therapy is the most common cause of adrenal insufficiency. The -diagnosis of adrenal insufficiency is made by -demonstrating low basal and/or stimulated serum cortisol and should be -followed by appropriate investigations to establish the -underlying aetiology. Maintenance glucocorticoid -replacement is usually given as a twice or thrice daily hydrocortisone preparation. Patients with primary adrenal insufficiency also require mineralocorticoid. Regular monitoring for features of under- and over- replacement is essential during follow-up. Patient education is a key feature of management of this condition.


Specific inhibition of hypoxia-inducible factor (HIF)-1 alpha activation and of vascular endothelial growth factor (VEGF) production by flavonoids.
Screening using a reporter under the control of the hypoxia-response element (HRE) identified several flavonoids and homoisoflavonoids that inhibit the activation of HRE under hypoxic conditions. Among various compounds, isorhamnetin, luteolin, quercetin, and methyl ophiopogonanone B (MOB) were effective at 3 to 9 microg/ml in inhibiting the reporter activity. The expression of vascular endothelial growth factor (VEGF) mRNA during hypoxia was also inhibited by MOB in HepG2 cells, but the effective doses were 10 to 20 microg/ml. MOB caused destabilization of hypoxia-inducible factor (HIF)-1alpha, as revealed by Western blotting, that was dependent on proteasome activity and the tumor suppressor, p53. The tubular formation and migration of human umbilical vein endothelial cells was also inhibited by MOB. MOB is expected to act as an inhibitor of angiogenesis.


Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her-2-neu, and GADD45 expression in oral squamous cell carcinoma.
Head and neck cancers are the commonest cancer in Southeast Asia. Despite being a surface cancer, it is associated with significant morbidity as despite early detection by the patients they often report for treatment late and hence are associated with poor prognosis. The role of neoadjuvant chemotherapy in head and neck cancer is still under evaluation; there is a large subgroup of population that does not respond to chemotherapy, and hence, most studies have failed to show any survival benefit. This study evaluated the role of neoadjuvant therapy with docetaxel and carboplatin in patients with oral cancer and correlated the response to human papilloma virus, EGFR1, EGFR2, and GADD45 expression. A total of 24 locally advanced, non-metastatic oral cancer patients were included in the study. Tumor biopsies were taken prior to the start of neoadjuvant therapy for expression of EGFR, Her-2-Neu, and GADD45 by immunohistochemistry and for HPV by PCR. The response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria after three cycles of chemotherapy. Statistical analysis was performed using correlation and Kaplan-Meier analysis; the difference in survival was calculated with log rank test. A total of 21 male and 3 female with a mean age of 53.12 years were enrolled. Sixty-five percent of these received three cycles of chemotherapy. Five patients were positive for HPV 16 and none for HPV 18. Twenty-two of 24 patients showed GADD45 expression, 3 showed expression of Her-2-Neu while all 24 showed expression for EGFR1 protein. Two-year overall survival was 81%; GADD45 expressions were found to significantly affect the overall and disease-free survival, while any of the other protein expression studied and HPV status was not significant. The result of the present study shows significant downgrading of the oral cancers with neoadjuvant chemotherapy suggesting its utility in borderline operable cases. However, the response of chemotherapy does not appear to be related to the expression of EGFR, Her-2-Neu, and GADD45 protein or presence of HPV. Bone involvement, perineural invasion, and GADD45 expression significantly predict OS and DFS. All patients who did not express Gadd45 died before 2 years. Study with more subjects and longer follow-up should be carried out to elucidate this relation further.


Slab2, a comprehensive subduction zone geometry model.
Subduction zones are home to the most seismically active faults on the planet. The shallow megathrust interfaces of subduction zones host Earth's largest earthquakes and are likely the only faults capable of magnitude 9+ ruptures. Despite these facts, our knowledge of subduction zone geometry-which likely plays a key role in determining the spatial extent and ultimately the size of subduction zone earthquakes-is incomplete. We calculated the three-dimensional geometries of all seismically active global subduction zones. The resulting model, called Slab2, provides a uniform geometrical analysis of all currently subducting slabs.


Endovascular treatment of Budd-Chiari syndrome with hepatic vein obstruction in China.
Abstract Purpose: To evaluate characteristics of obstructions of the hepatic veins (HVs) in Chinese patients, technical aspects of puncture of the HVs, short- and mid-term outcomes, and complications of endovascular treatment. Forty-eight HV patients with different degrees of symptoms and signs of portal hypertension were enrolled in our study. Endovascular treatments with balloon and stents were performed. Catheter-directed thrombolysis (CDT) was performed in patients with thrombosis in the HVs. For patients with lesions of both the HVs and the inferior vena cava (IVC), balloon expansions or stenting were performed at the IVC lesions also. Endovascular treatments were successful in 43 patients. The technically success rate was 89.6% (43/48). Fifteen patients underwent solely balloon expansions, 28 patients had balloon expansions and stentings, 5 patients underwent CDT, and 3 patients had implanted stents in the IVC lesions at the same time. The symptoms of portal hypertension were alleviated in 39 patients postoperatively. In the other 4 cases portal hypertension was mildly alleviated at discharge. Thirty-nine of the 43 patients were followed up for an average of 24±1.3 months (range, 6-62 months). Ascites were completely resolved in 32 cases, with a small amount of ascites in 4 patients and moderate to massive amounts in 3 patients. Hepatomegaly and splenomegaly completely disappeared in 30 patients and still could be touched in 6 patients. The HVs were patent in 29 patients. Restenosis and re-occlusion of the HVs appeared in 4 cases. All patients were successfully treated by endovascular treatments. Endovascular treatments for patients with obstruction of the HVs have a high technical success rate, fewer complications, and better short- and mid-term clinical outcome. The key to successful endovascular treatment is successful puncture of HVs. For patients who have occlusive lesions of HVs combined with occlusive IVC, recanalization of the lesions of the HVs could achieve good results.


A comparative study of isolation-induced ultrasonic vocalization in rodent pups.
The purpose of this study was to determine whether species differences in neonatal vocalizations of rodent pups could be observed. Ultrasonic vocalizations of pups of 5 rodent species, mouse (ICR), vole (Microtus arvalis), Syrian hamster, rat (Wistar-Imamichi), and Mongolian gerbil were recorded from 3 to 15 or 21 days of age. Recordings were made under conditions of separation from mothers and litter mates in a cooled chamber (approximately 10 degrees C). The major species differences observed were age specific and species specific frequencies. The Mongolian gerbil displayed a different frequency change with age. Namely, the day on which ultrasonic vocalizations ceased was delayed in Mongolian gerbil compared with the other rodents. The modal peak frequencies of ultrasound emitted from pups at 3 days of age were low (around 35 kHz) in the vole and the Syrian hamster, medium (around 45 kHz) in the rat and the Mongolian gerbil, and high (around 55 kHz) in the mouse.


Ecological indicators reveal historical regime shifts in the Black Sea ecosystem.
The Black Sea is one of the most anthropogenically disturbed marine ecosystems in the world because of introduced species, fisheries overexploitation, nutrient enrichment via pollution through river discharge, and the impacts of climate change. It has undergone significant ecosystem transformations since the 1960s. The infamous anchovy and alien warty comb jelly Mnemiopsis leidyi shift that occurred in 1989 is the most well-known example of the drastic extent of anthropogenic disturbance in the Black Sea. Although a vast body of literature exists on the Black Sea ecosystem, a holistic look at the multidecadal changes in the Black Sea ecosystem using an ecosystem- and ecology-based approach is still lacking. Hence, this work is dedicated to filling this gap. First, a dynamic food web model of the Black Sea extending from 1960 to 1999 was established and validated against time-series data. Next, an ecological network analysis was performed to calculate the time series of synthetic ecological indicators, and a regime shift analysis was performed on the time series of indicators. The model successfully replicated the regime shifts observed in the Black Sea. The results showed that the Black Sea ecosystem experienced four regime shifts and was reorganized due to effects instigated by overfishing in the 1960s, eutrophication and establishment of trophic dead-end organisms in the 1970s, and overfishing and intensifying interspecies trophic competition by the overpopulation of some r-selected organisms (i.e., jellyfish species) in the 1980s. Overall, these changes acted concomitantly to erode the structure and function of the ecosystem by manipulating the food web to reorganize itself through the introduction and selective removal of organisms and eutrophication. Basin-wide, cross-national management efforts, especially with regard to pollution and fisheries, could have prevented the undesirable changes observed in the Black Sea ecosystem and should be immediately employed for management practices in the basin to prevent such drastic ecosystem fluctuations in the future.


Controllable synthesis of ordered mesoporous NiFe₂O₄ with tunable pore structure as a bifunctional catalyst for Li-O₂ batteries.
Three-dimensional ordered mesoporous (3DOM) NiFe2O4 materials with tunable pore size ranging from 5.0 to 25.1 nm have been synthesized via a hard template and used as bifunctional electrocatalysts for rechargeable Li-O2 batteries. Characterization of the catalysts by X-ray diffraction and transmission electron microscopy confirms the formation of a single-phase 3DOM NiFe2O4 structure. Linear scanning voltammetry measurements reveal that Ketjen black (KB) carbon-supported 3DOM NiFe2O4 exhibits a decreased overpotential for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) than commonly used KB. A reduction in both the ORR and OER overpotentials increases with the mean pore size of 3DOM NiFe2O4 materials. Importantly, Li-O2 batteries with 3DOM NiFe2O4 materials as the cathode catalysts exhibit a significant enhancement in the discharge capacity, rate capability, and cyclability, and these performances increases with the mean pore size of 3DOM NiFe2O4 materials. For a Li-O2 battery equipped with a 3DOM NiFe2O4 catalyst with a maximum mean pore size of 25.1 nm, a long cycling life of up to 100 cycles under the limiting capacity of 1000 mAh gC(-1) is achieved, strongly indicating that the mesoporous size of the bifunctional catalysts plays a crucial role in enhancing the performance of Li-O2 batteries. The combined use of 3DOM NiFe2O4 with a maximal pore size of 25.1 nm and a poly(vinylidene difluoride hexafluoropropylene) separator with a tuned pore structure further improves the Li-O2 battery performance, highlighting the importance of the pore structure in the development of bifunctional catalysts and separators.


Biomarkers for the early detection of relapses in metastatic colorectal cancers.
To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), β2-microglobulin (β2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, β2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.


Evaluation of processed bovine cancellous bone matrix seeded with syngenic osteoblasts in a critical size calvarial defect rat model.
Biologic bone substitutes may offer alternatives to bone grafting procedures. The aim of this study was to evaluate a preformed bone substitute based on processed bovine cancellous bone (PBCB) with or without osteogenic cells in a critical size calvarial defect rat model. Discs of PBCB (Tutobone) were seeded with second passage fibrin gel-immobilized syngenic osteoblasts (group A, n = 40). Cell-free matrices (group B, n = 28) and untreated defects (group C; n=28) served as controls. Specimens were explanted between day 0 and 4 months after implantation and were subjected to histological and morphometric evaluation. At 1 month, bone formation was limited to small peripheral areas. At 2 and 4 months, significant bone formation, matrix resorption as well as integration of the implants was evident in groups A and B. In group C no significant regeneration of the defects was observed. Morphometric analysis did not disclose differences in bone formation in matrices from groups A and B. Carboxyfluorescine-Diacetate-Succinimidylester (CFDA) labeling demonstrated low survival rates of transplanted cells. Osteoblasts seeded into PBCB matrix display a differentiated phenotype following a 14 days cell culture period. Lack of initial vascularization may explain the absence of added osteogenicity in constructs from group A in comparison to group B. PBCB is well integrated and represents even without osteogenic cells a promising biomaterial for reconstruction of critical size calvarial bone defects.


[Treat Princes in Cordoue (9th-10th centuries)].
It is proposed, through biographic notes and historical reports, to observe the physicians/power relationships in one hand, and power/medical institutions relationships on the other, in Cordoue, during omeyades' emirate and caliphate, between the 9th and 10th centuries. The gathered information allows to describe the social position of physicians who received marks of favor from princes, but also served the power in place for various responsabilities. These documents are also able to make an evaluation of the role of princes for the development of medico-pharmaceutical subjects and give indications on the health of great figures, on their diseases and the conditions of their death.


Adipokine gene expression in brain and pituitary gland.
The brain has been recognized as a prominent site of peptide biosynthesis for more than 30 years, and many neuropeptides are now known to be common to gut and brain. With these precedents in mind it is remarkable that adipose-derived peptides like leptin have attracted minimal attention as brain-derived putative neuromodulators of energy balance. This review outlines the evidence that several adipose-specific genes are also expressed in the central nervous system and pituitary gland. We, and others, confirmed that the genes for leptin, resistin, adiponectin, FIAF (fasting-induced adipose factor) and adiponutrin are expressed and regulated in these tissues. For example, leptin mRNA was readily detectable in human, rat, sheep and pig brain, but not in the mouse. Leptin expression in rat brain and pituitary was regulated through development, by food restriction, and following traumatic brain injury. In contrast, hypothalamic resistin mRNA was unaffected by age or by fasting, but was significantly depleted by food restriction in mouse pituitary gland. Similar results were seen in the ob/ob mouse, and we noted a marked reduction in resistin-positive hypothalamic nerve fibres. Resistin and fiaf mRNA were also upregulated in hypoxic/ischaemic mouse brain. Our studies on the regulation of neuronal adipokines were greatly aided by the availability of clonal hypothalamic neuronal cell lines. One of these, N-1, expresses both rstn and fiaf together with several other neuropeptides and receptors involved in energy homeostasis. Selective silencing of rstn revealed an autocrine/paracrine regulatory system, mediated through socs-3 expression that may influence the feedback effects of insulin and leptin in vivo. A similar convergence of signals in the pituitary gland could also influence anterior pituitary hormone secretion. In conclusion, the evidence is suggestive that brain and pituitary-derived adipokines represent a local regulatory circuit that may fine tune the feedback effects of adipose hormones in the control of energy balance.


Memory impairment after mild traumatic brain injury.
Concerns of memory impairment are common after mild traumatic brain injury (mTBI). Acute effects after mTBI may include posttraumatic amnesia, which may last up to 24 hours. In the postacute phase, memory concerns are usually linked with increased distractibility; impaired attention, working memory, retrieval; and executive dysfunction. These acute and postacute impairments have distinct neuroanatomic and pathophysiologic correlates. Cognitive assessment should be undertaken during the acute phase after an mTBI using a standardized tool that can be administered quickly and is sensitive to cognitive impairment. Early validation of the patient's symptoms and concerns (especially the expectation of recovery), coupled with educational and emotional support after the mTBI, remains the core approach to treatment. The effects of comorbidities, recurrent mTBIs, and blast exposures in military personnel on protracted symptoms and long-term cognitive deficits will be discussed.


Molybdenum and tungsten promoted carbons for use as catalyst supports in methanol electro-oxidation.
Two types of the molybdenum and tungsten promoted carbons (MWCs) were prepared by the successive impregnation and co-impregnation of molybdenum and tungsten precursors on carbon black with a heat treatment. The resulting MWCs were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and electrochemical techniques and evaluated as a catalyst support for a Pt catalyst in methanol electro-oxidation. MWC-S, prepared by successive impregnation, showed a well developed carbidic phase with a large portion of tungsten carbide phase. In contrast, MWC-C, prepared by co-impregnation, had a lower amount of carbidic carbon and larger fraction of molybdenum carbide phase. MWCs-supported Pt catalysts showed higher catalytic activities than the Pt catalyst on pure carbon black in both CO oxidation and methanol electro-oxidation. In particular, Pt/MWC-S exhibited the highest performance among the Pt catalysts employed in this work. The high activity of Pt/MWC-S can be attributed to the positive effect of molybdenum-tungsten carbide phase, which promotes the activation of water and the removal of intermediate CO species.


Development of a polymerase chain reaction method for diagnosing Babesia gibsoni infection in dogs.
A pair of oligonucleotide primers were designed according to the nucleotide sequence of the P18 gene of Babesia gibsoni (B. gibsoni), NRCPD strain, and were used to detect parasite DNA from blood samples of B. gibsoni-infected dogs by polymerase chain reaction (PCR). PCR was specific for B. gibsoni since no amplification was detected with DNA from B. Canis or normal dog leucocytes. PCR was sensitive enough to detect parasite DNA from 2.5 microl of blood samples with a parasitemia of 0.000002%. PCR detected parasite DNA from 2 to 222 days post-infection in sequential blood samples derived from a dog experimentally infected with B. gibsoni. The detection of B. gibsoni DNA by PCR was much earlier than the detection of antibodies to B. gibsoni in blood samples by the indirect fluorescent antibody test (IFAT) or that of the parasite itself in Giemsa-stained thin blood smear film examined by microscopy. In addition, 28 field samples collected from dogs in Kansai area, Japan, were tested for B. gibsoni infection. Nine samples were positive in blood smears, 9 samples were positive by IFAT and 11 samples were positive for B. gibsoni DNA by PCR. The nucleotide sequences of PCR products from all 11 samples found positive by PCR were completely identical to that of the P18 gene of the B. gibsoni, NRCPD strain. These results suggest that PCR provides a useful diagnostic tool for the detection of B. gibsoni infection in dogs.


"End-stage kidney" in longstanding bulimia nervosa.
The extent of renal damage over long-term binge/purges has not been well documented in bulimia nervosa (BN). We describe a 52-year-old woman with longstanding BN subsequent to an 8-year history of anorexia nervosa (AN). The patient showed chaotic binge/purges and chronic severe hypokalemia after recovery from AN at age 26 years, and renal biopsy showed juxtaglomerular hyperplasia, which was diagnosed as pseudo-Bartter's syndrome. Over the following 26 years, the patient's eating behaviors remained chaotic, and her renal function gradually deteriorated. After the patient died of pneumonia and sepsis at age 52 years, autopsy of her kidney showed chronic interstitial nephritis, proximal tubular swelling, and diffuse glomerular sclerosis, suggesting chronic glomerular injury associated with long-term binge/purges. To our knowledge, this is the first case report of a patient with BN with long-term binge/purges who developed an eventual "end-stage kidney" characterized by hypokalemic nephropathy and diffuse glomerulosclerosis.


[Changes in visually evoked potentials in space-occupying processes of the posterior fossa--on the problem of ascending transtentorial herniation].
Through the use of VEP investigations in 82 patients with space occupying lesions in the infratentorial region this study attempts to find the cause and location of dysfunctions of optical signal pathways. The majority of such expandatory processes involved tumours exterior to the brainstem of inhomogeneous histomorphology (n = 65). The rest involved metastases of the cerebellum (n = 5) and expanding infarcts of one cerebellar hemisphere (n = 12). Besides a shifting of the 4th ventricle (n = 64) an accompanying hydrocephalus (n = 40) and an ascending transtentorial herniation (n = 29) was indicated radiologically. A pathological VEP was found in just over half of the patients (n = 43). Usually, the VEP change involved a latency increase of the cortical potential (P2). In 6 of these patients a complete loss of this potential was noted. Furthermore, ten more of these patients did not have the P1-following negative potential (N2). In 32 patients with a pathological VEP a hydrocephalus was proven to be present. On the other hand, there were 8 patients with accompanying hydrocephalus but with a normal VEP. All 29 patients, though, with a radiological ascending herniation had changed VEP. Three of these patients had no accompanying hydrocephalus. Following surgical decompression a complete normalization of the VEP set within 2 to 3 weeks, while it reappeared in tumour recurrence. These findings indicate that dysfunctions of VEP, that is the visual pathways in infratentorial occupying lesions are not only dependent on the existence of accompanying hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS)


Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.
This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable.


Techniques for restoring worn anterior teeth with direct composite resin.
Toothwear is increasing in prevalence. Traditional treatment methods for moderate or advanced toothwear, such as indirect restorations and crown lengthening surgery, are invasive and destructive of remaining tissues. The 'Dahl technique' has been used to obtain space for anterior restorations and has been modified such that direct composite restorations are placed at increased occlusal vertical dimension. These restorations have proved durable and aesthetic, protect tooth structure and posterior occlusal contact is predictably re-established. The authors describe and compare two techniques using composite resin to treat localized anterior toothwear in a general practice setting. Toothwear is a significant clinical problem and general dental practitioners and specialists alike must be familiar with the available conservative treatment options.


Physical Activity Assessment During Gestation and Its Outcomes: A Review.
Physical activity recommendations emphasize a positive influence of exercise on health. It is particularly recognized during pregnancy for both the mother and fetus. This review aims to identify the main trends of activity undertaken by women during gestation and to find out how it affects the expecting mother and her child. Review of the literature comprising the following databases: PubMed, Academic Search Complete, Health Source-Consumer Edition, Health Source: Nursing/Academic Edition, EMBASE (2000 to May 2013), used detailed search strategies. The review was restricted to experimental studies. Trials were excluded if they met any of the following criteria: reviews, letters, commentaries or editorials, only abstracts available, and any kind of pathology during pregnancy. Three assessors reviewed the titles, abstracts, and full articles using standardized data abstraction forms, and they assessed the study quality. A total of 474 potential articles remained for analyses. Twenty-eight articles were eligible for inclusion in the present review: randomized controlled trials and observational studies that evaluated maternal and offspring outcomes as a result of physical activity during pregnancy. Quasi-randomized trials were excluded. The activities that were most frequently assessed included occupational activity, housework/caregiving, sport/exercise, and active living, as well as habits. The authors evaluated different types of physical activity in the loading conditions. The aerobic activities most frequently used for assessment included treadmill walking program; step aerobics or stair stepper; aerobics; bicycle ergometer; combination of rowing, stationary cycling, and walk jogging; rhythmic calisthenics class and step class; brisk walks; stretching; and relaxation. The benefits following being active during pregnancy are associated with improved maternal psychological well-being, a reduced risk of preterm birth and excessive gestational weight gain, and lower risk of birth-related complications. Patterns of activity change during pregnancy. Although exercise is safe for both the mother and fetus, most women reduce their activity level during the first weeks of gestation. Specifically, physical activity tends to be of lower duration, frequency, and intensity. Therefore, women should be encouraged by professionals to initiate or continue exercising during a healthy pregnancy.


Administering and monitoring high-alert medications in acute care.
The nurse's primary role in the medication process is to ensure that drugs are administered safely to patients, thus reducing the risk of unnecessary harm or injury. High-alert medications are a particular concern for healthcare professionals, since they are associated with an increased risk of causing patient harm. This article identifies high-risk medications and outlines measures that can be used to prevent potential harm to patients as a result of these medications, including computerised provider order entry, Tall Man lettering, order sets, independent double-checks and proactive patient monitoring.


Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney.
We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.


Comparison between efficacy of MDI+spacer and nebuliser in the management of acute asthma in children.
Due to changing evidence on efficacy of MDI+spacer as compared to nebuliser, two types of managements were going on in our Day unit, depending on the presence of different medical professionals. We wanted to find out the evidence of the best practice from within our unit, and then to formulate guidelines based on it for the management of paediatric acute asthma. We isolated 54 cases of children suffering from acute asthma attack from admissions during Oct 2004-March 2005 within the age range of 3-14 yrs. We categorised them into four classes of mild, moderate, severe and life threatening acute attack depending on its severity and then separated them in two groups. Group I received salbutamol Via MDI+spacer and Group II received salbutamol via nebuliser. Our outcome measure was time to clinical improvement and duration of hospital stay. We didn't find any major difference between the two groups, moreover MDI+spacer was better than nebuliser for the treatment of severe acute asthma attack in children. Our study supported and confirmed the evidence that MDI+spacer is least as effective as nebuliser in the management of acute asthma in children.


Expression of functional GABAA receptors in transfected L929 cells isolated by immunomagnetic bead separation.
Transient cotransfection of fibroblasts, with plasmids encoding individual GABAA receptor (GABAAR) subunits, has provided a model to characterize the pharmacological and kinetic properties of receptor subtype combinations. However, identifying transfected cells for electrophysiological recording is often difficult due to low transfection efficiencies. Selection of transfected cells has required cotransfection with a marker gene and fluorescence microscopic localization prior to recording. To circumvent these problems, two GABAAR subtypes combinations in transfected L929 cells were isolated with a novel biomagnetic separation system. Cell selection was accomplished by cotransfection with a plasmid (pHook-1) encoding a single-stranded cell surface antibody (sFv), which bound to ferromagnetic beads, coated with an antigen (phOx). Bead-covered cells were then magnetically separated from non-transfected cells. Bead-selected cells cotransfected with alpha 6, beta 3 and gamma 2L subtypes, expressed GABAAR currents in 95% (41/43) of cells recorded. Cells cotransfected with alpha 5, beta 3 and gamma 2L subtypes had an EC50 for GABA of 5.4 microM and a Hill slope of 1.4. Membrane patches from cells expressing the alpha 5 beta 3 gamma 2L isoform demonstrated single channel currents with a main conductance state of 23 pS. Magnetic bead immunoselection provides a purified population of transfected cells well suited for whole cell and single channel recording.


Antimicrobial action of hydrolyzed chitosan against spoilage yeasts and lactic acid bacteria of fermented vegetables.
The antimicrobial properties of various chitosan-lactate polymers (ranging from 0.5 to 1.2 MDa in molecular weight) against two yeasts isolated from fermented vegetables and against three lactic acid bacteria from a mixed starter for sauerkraut on methylene blue agar (MBA) and in vegetable juice medium (VJM) were investigated. Chitosan-lactate reduced the growth of all microorganisms in solid (MBA) as well as in liquid (VJM) medium. In MBA, a concentration of 5 g/liter was needed to inhibit the growth of Saccharomyces bayanus, while 1 g/liter was sufficient to inhibit the growth of Saccharomyces unisporus. Lactic acid bacteria were also inhibited in this range of concentrations. The low-molecular-weight chitosan-lactate DP3 (0.5 kDa) was most efficient in solid medium (MBA), and inhibitory activities decreased with increasing hydrolysate lengths. In liquid medium (VJM), 0.5 g of chitosan-lactate per liter reduced the growth rates for both yeasts, but 10 g/liter was insufficient to prevent yeast growth. Intermediate-molecular-weight chitosan-lactate (5 kDa) was more efficient than chitosan of low molecular weight. Native chitosan (1.2 MDa) showed no inhibition in either medium. Microscopic examination of S. unisporus Y-42 after treatment with chitosan-lactate DP25 showed agglutination of a refractive substance on the entire cell wall, suggesting an interaction between chitosan and the cell wall. When chitosanase was added to the culture media containing chitosan-lactate, refractive substances could not be observed.


The first cavefish in the Dinaric Karst? Cave colonization made possible by phenotypic plasticity in Telestes karsticus.
Cave animals are an excellent model system for studying adaptive evolution. At present, however, little is known about the mechanisms that enable surface colonizers to survive in the challenging environment of caves. One possibility is that these species have the necessary genetic background to respond with plastic changes to the pressures of underground habitats. To gain insight into this process, we conducted a comparative study with the fish species Telestes karsticus, which occurs in a hydrological system consisting of an interconnected stream and a cave. Results showed that T. karsticus resided year-round and spawned in Sušik cave, making it the first known cavefish in the Dinaric Karst. Cave and surface populations differed in morphological and physiological characteristics, as well as in patterns of gene expression without any evidence of genetic divergence. To test whether observed trait differences were plastic or genetic, we placed adult fish from both populations under light/dark or constant dark conditions. Common laboratory conditions erased all morphometric differences between the two morphs, suggesting phenotypic plasticity is driving the divergence of shape and size in wild fish. Lighter pigmentation and increased fat deposition exhibited by cave individuals were also observed in surface fish kept in the dark in the laboratory. Our study also revealed that specialized cave traits were not solely attributed to developmental plasticity, but also arose from adult responses, including acclimatization. Thus, we conclude that T. karsticus can adapt to cave conditions, with phenotypic plasticity playing an important role in the process of cave colonization.


Taste perception and diet in people of Chinese ancestry.
Taste perception plays a key role in consumer acceptance and food choice, which has an important impact on human health. Our aim was to examine the relationship between taste intensities and preferences of sweet (sucrose), salty (sodium chloride and potassium chloride), sour (citric acid), and bitter (quinine and phenylthiocarbamide) in relation to dietary intake and dietary patterns in people of Chinese ancestry. This cross-sectional study included 100 adult Singaporean Chinese (50 women). A validated taste methodology was used with taste solutions provided by Monell Chemical Senses Center. Dietary intake and patterns were assessed by dietary recalls. There was little relationship between taste intensity and tastant preference in regard to background dietary intake or pattern. Tastant differentiation was reliable, but there was some confusion in regard to the rating of saltiness as sourness. There was a salty-sour confusion among Singaporean Chinese unlike the bitter-sour confusion reported for Caucasians. Most sodium came from sauces and was added during food preparation. In programs to address sodium: potassium ratio excess among Chinese prone to hypertension and stroke, sour as well as salty taste may need to be considered.


Intratumoral heterogeneity characterized by pretreatment PET in non-small cell lung cancer patients predicts progression-free survival on EGFR tyrosine kinase inhibitor.
Intratumoral heterogeneity has been suggested to be an important resistance mechanism leading to treatment failure. We hypothesized that radiologic images could be an alternative method for identification of tumor heterogeneity. We tested heterogeneity textural parameters on pretreatment FDG-PET/CT in order to assess the predictive value of target therapy. Recurred or metastatic non-small cell lung cancer (NSCLC) subjects with an activating EGFR mutation treated with either gefitinib or erlotinib were reviewed. An exploratory data set (n = 161) and a validation data set (n = 21) were evaluated, and eight parameters were selected for survival analysis. The optimal cutoff value was determined by the recursive partitioning method, and the predictive value was calculated using Harrell's C-index. Univariate analysis revealed that all eight parameters showed an increased hazard ratio (HR) for progression-free survival (PFS). The highest HR was 6.41 (P<0.01) with co-occurrence (Co) entropy. Increased risk remained present after adjusting for initial stage, performance status (PS), and metabolic volume (MV) (aHR: 4.86, P<0.01). Textural parameters were found to have an incremental predictive value of early EGFR tyrosine kinase inhibitor (TKI) failure compared to that of the base model of the stage and PS (C-index 0.596 vs. 0.662, P = 0.02, by Co entropy). Heterogeneity textural parameters acquired from pretreatment FDG-PET/CT are highly predictive factors for PFS of EGFR TKI in EGFR-mutated NSCLC patients. These parameters are easily applicable to the identification of a subpopulation at increased risk of early EGFR TKI failure. Correlation to genomic alteration should be determined in future studies.